Emerging multisystem biomarkers in hereditary transthyretin amyloidosis: a pilot study.

Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score). Blood samples were collected from 16 patients diagnosed with ATTRv amyloidosis and a verified TTR variant and from 26 healthy controls. ATTRv patients were stratified by clinical phenotype (neurologic vs. mixed), genotype (V30M vs. non-V30M), and disease severity. We found significantly higher levels of serum GDF-15 in ATTRv patients compared with controls. Mean serum Umod levels were significantly lower in patients with ATTRv than controls. A positive correlation was found between serum Umod and estimated glomerular filtration rate (eGFR), while an inverse correlation was found with cystatin C levels. Conversely, GDF-15 showed a negative correlation with eGFR, and a direct correlation with cystatin C levels. No correlation was demonstrated between GDF-15 or Umod levels and traditional cardiac biomarkers. The results identify alteration of serum levels of GDF-15 and Umod in ATTRv amyloidosis.

MOREOVER: multiomics MR-guided radiotherapy optimization in locally advanced rectal cancer.

BACKGROUND: Complete response prediction in locally advanced rectal cancer (LARC) patients is generally focused on the radiomics analysis of staging MRI. Until now, omics information extracted from gut microbiota and circulating tumor DNA (ctDNA) have not been integrated in composite biomarkers-based models, thereby omitting valuable information from the decision-making process. In this study, we aim to integrate radiomics with gut microbiota and ctDNA-based genomics tracking during neoadjuvant chemoradiotherapy (nCRT). METHODS: The main hypothesis of the MOREOVER study is that the incorporation of composite biomarkers with radiomics-based models used in the THUNDER-2 trial will improve the pathological complete response (pCR) predictive power of such models, paving the way for more accurate and comprehensive personalized treatment approaches. This is due to the inclusion of actionable omics variables that may disclose previously unknown correlations with radiomics. Aims of this study are: - to generate longitudinal microbiome data linked to disease resistance to nCRT and postulate future therapeutic strategies in terms of both type of treatment and timing, such as fecal microbiota transplant in non-responding patients. - to describe the genomics pattern and ctDNA data evolution throughout the nCRT treatment in order to support the prediction outcome and identify new risk-category stratification agents. - to mine and combine collected data through integrated multi-omics approaches (radiomics, metagenomics, metabolomics, metatranscriptomics, human genomics, ctDNA) in order to increase the performance of the radiomics-based response predictive model for LARC patients undergoing nCRT on MR-Linac. EXPERIMENTAL DESIGN: The objective of the MOREOVER project is to enrich the phase II THUNDER-2 trial (NCT04815694) with gut microbiota and ctDNA omics information, by exploring the possibility to enhance predictive performance of the developed model. Longitudinal ctDNA genomics, microbiome and genomics data will be analyzed on 7 timepoints: prior to nCRT, during nCRT on a weekly basis and prior to surgery. Specific modelling will be performed for data harvested, according to the TRIPOD statements. DISCUSSION: We expect to find differences in fecal microbiome, ctDNA and radiomics profiles between the two groups of patients (pCR and not pCR). In addition, we expect to find a variability in the stability of the considered omics features over time. The identified profiles will be inserted into dedicated modelling solutions to set up a multiomics decision support system able to achieve personalized treatments.

Uterus motion analysis for radiotherapy planning optimization. The innovative contribution of on-board hybrid MR imaging.

Introduction: Organ motion (OM) and volumetric changes pose challenges in radiotherapy (RT) for locally advanced cervical cancer (LACC). Magnetic Resonance-guided Radiotherapy (MRgRT) combines improved MRI contrast with adaptive RT plans for daily anatomical changes. Our goal was to analyze cervico-uterine structure (CUS) changes during RT to develop strategies for managing OM. Materials and methods: LACC patients received chemoradiation by MRIdian system with a simultaneous integrated boost (SIB) protocol. Prescription doses of 55-50.6 Gy at PTV1 and 45-39.6 Gy at PTV2 were given in 22 and 25 fractions. Daily MRI scans were co-registered with planning scans and CUS changes were assessed.Six PTVs were created by adding 0.5, 0.7, 1, 1.3, 1.5, and 2 cm margins to the CUS, based on the simulation MRI. Adequate margins were determined to include 95 % of the CUSs throughout the entire treatment in 95 % of patients. Results: Analysis of 15 LACC patients and 372 MR scans showed a 31 % median CUS volume decrease. Asymmetric margins of 2 cm cranially, 0.5 cm caudally, 1.5 cm posteriorly, 2 cm anteriorly, and 1.5 cm on both sides were optimal for PTV, adapting to CUS variations. Post-14th fraction, smaller margins of 0.7 cm cranially, 0.5 cm caudally, 1.3 cm posteriorly, 1.3 cm anteriorly, and 1.3 cm on both sides sufficed. Conclusion: CUS mobility varies during RT, suggesting reduced PTV margins after the third week. MRgRT with adaptive strategies optimizes dose delivery, emphasizing the importance of streamlined IGRT with reduced PTV margins using a tailored MRgRT workflow with hybrid MRI-guided systems.

Impact of body composition parameters on radiation therapy compliance in locally advanced rectal cancer: A retrospective observational analysis.

Background: The impact of body composition and sarcopenia in locally advanced rectal cancer (LARC) is still unclear, even several studies have been published on this issue. Our study aims to analyze the impact of sarcopenia on neoadjuvant chemoradiotherapy (nCRT) tolerance and survival outcomes. Methods: This is a retrospective, monocentric study where LARC patients treated between 2010 and 2020 were enrolled. A single slice, from the pre-therapy simulation computed tomography (CT) scan, was used to perform the body composition analysis with dedicated software. The primary endpoint was the impact of body composition on radiotherapy (RT) interruption secondarily on overall survival (OS), disease-free survival (DFS), and local control (LC). Results: The study included 628 LARC patients (40.9 % female, mean age 63.4 years): 24 % had low skeletal muscle index (SMI), 30 % had low muscle density (MD) and 17 (10.3 % of obese) were sarcopenic obese. Higher BMI (OR 2.38, 95 % CI 1.36-4.01) and lower SMI (0.73, 95 % CI 0.55-0.94) resulted as independent predictors of RT interruption. Sarcopenic obesity (HR 2.83, 95 % CI 1.24-6.45) was related to worse OS, while MD (0.96, 95 % CI 0.93-0.98), and higher SMI (0.97, 95 % CI 0.95-0.99) were related to better OS; a lower MD remained also associated even in adjusted multivariable analysis (0.96, 95 % CI0.93-0.98). Moreover, higher visceral adipose tissue (VAT) resulted associated with worse DFS (1.02, 95 % CI 1.01-1.03), while higher SMI was related to better Local Control (0.96, 95 % CI 0.93-0.99). Conclusions: Body composition analysis, particularly of muscle and fat masses, may be a useful tool for better management of LARC patients undergoing RT. Increased collaboration between radiation oncologists and clinical nutritionists is advisable, to enable early nutritional support of LARC.

Serum neurofilament light chain levels correlate with small fiber related parameters in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

BACKGROUND: Recent evidence suggests that both serum neurofilament light chain (sNfL) levels and small fiber related diagnostic variables may be valuable disease biomarkers of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). Our study aimed to explore the relations between sNfL and small fiber related skin biopsy and quantitative sensory testing (QST) parameters in a cohort of ATTRv-PN patients and pre-symptomatic carriers. METHODS: We retrospectively analyzed data from 13 ATTRv patients and 21 pre-symptomatic carriers who underwent sNfL dosage, skin biopsy, and QST, and analyzed correlations between sNFL, intraepidermal nerve fiber density (IENFD), and cold (CDT) and warm detection thresholds (WDT). RESULTS: Both sNfL and small fiber related parameters significantly differed between carriers and patients (sNfL: p < 0.0001; IENFD: p = 0.0008; CDT, WDT: < 0.0001). sNFL levels were normal in all carriers, altered in 85% of patients, negatively correlated with distal IENFD (r = -0.47, p = 0.005), and significantly correlated with CDT (r = -0.68; p < 0.0001) and WDT (r = 0.57; p < 0.0001). CONCLUSIONS: Our study showed that sNfL reliably discriminates symptomatic ATTRv-PN patients from pre-symptomatic carriers, and found significant relations between sNfL, skin biopsy, and QST small fiber related parameters, suggesting that sNfL might be a valuable biomarker of peripheral nerve involvement in ATTRv-PN and a supportive criterion for symptomatic disease transition.

Neoadjuvant treatment of colorectal cancer: comprehensive review.

BACKGROUND: Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery. METHODS: A narrative review of the most recent relevant literature was conducted. RESULTS: Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients. CONCLUSION: Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.

Long-term treatment of hereditary transthyretin amyloidosis with patisiran: multicentre, real-world experience in Italy.

BACKGROUND: Hereditary transthyretin (ATTRv, v for variant) amyloidosis with polyneuropathy is a rare disease caused by mutations in the transthyretin gene. In ATTRv amyloidosis, multisystem extracellular deposits of amyloid cause tissue and organ dysfunction. Patisiran is a small interfering RNA molecule drug that reduces circulating levels of mutant and wild-type TTR proteins. Prior to its regulatory approval, patisiran was available in Italy through a compassionate use programme (CUP). The aim of this study was to analyse the long-term outcomes of patients who entered into the CUP. METHODS: This was a multicentre, observational, retrospective study of patients with ATTRv amyloidosis treated with patisiran. The analysis included change from baseline to 12, 24, 36 and 48 months in familial amyloid polyneuropathy (FAP) stage, polyneuropathy disability (PND) class, neuropathy impairment score (NIS), modified body mass index (mBMI), Compound Autonomic Dysfunction Test (CADT), Karnofsky Performance Status (KPS) scale and Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire. Safety data were also analysed. RESULTS: Forty patients from 11 Italian centres were enrolled: 23 in FAP 1 (6 in PND 1 and 17 in PND 2) and 17 in FAP 2 (8 in PND 3a and 9 in PND 3b) stage. In this population, the mean NIS at baseline was 71.4 (± 27.8); mBMI, 917.1 (± 207) kg/m2; KPS, 67.1 (± 14.0); Norfolk QoL-DN, 62.2 (± 25.2); and CADT, 13.2 (± 3.3). Statistical analysis showed few significant differences from baseline denoting disease stability. No new safety signals emerged. CONCLUSIONS: Patisiran largely stabilised disease in patients with ATTRv amyloidosis.

Impact of data transfer between treatment planning systems on dosimetric parameters.

PURPOSE: In radiotherapy it is often necessary to transfer a patient's DICOM (Digital Imaging and COmmunications in Medicine) dataset from one system to another for re-treatment, plan-summation or registration purposes. The aim of the study is to evaluate effects of dataset transfer between treatment planning systems. MATERIALS AND METHODS: Twenty-five patients treated in a 0.35T MR-Linac (MRidian, ViewRay) for locally-advanced pancreatic cancer were enrolled. For each patient, a nominal dose distribution was optimized on the planning MRI. Each plan was daily re-optimized if needed to match the anatomy and exported from MRIdian-TPS (ViewRay Inc.) to Eclipse-TPS (Siemens-Varian). A comparison between the two TPSs was performed considering the PTV and OARs volumes (cc), as well as dose coverages and clinical constraints. RESULTS: From the twenty-five enrolled patients, 139 plans were included in the data comparison. The median values of percentage PTV volume variation are 10.8 % for each fraction, while percentage differences of PTV coverage have a mean value of -1.4 %. The median values of the percentage OARs volume variation are 16.0 %, 7.0 %, 10.4 % and 8.5 % for duodenum, stomach, small and large bowel, respectively. The percentage variations of the dose constraints are 41.0 %, 52.7 % and 49.8 % for duodenum, stomach and small bowel, respectively. CONCLUSIONS: This study has demonstrated a non-negligible variation in size and dosimetric parameters when datasets are transferred between TPSs. Such variations should be clinically considered. Investigations are focused on DICOM structure algorithm employed by the TPSs during the transfer to understand the cause of such variations.

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study.

BACKGROUND: Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification. METHODS: We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2). RESULTS: Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24-50 Gy, mean BEDα/ß10=93), while 41 Gy (range 16-50 Gy, mean BEDα/ß10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1-10 Gy) and 3,7 Gy (range 1,6-8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%. CONCLUSIONS: MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Impact of bias field correction on 0.35 T pelvic MR images: evaluation on generative adversarial network-based OARs' auto-segmentation and visual grading assessment.

Purpose: Magnetic resonance imaging (MRI)-guided radiotherapy enables adaptive treatment plans based on daily anatomical changes and accurate organ visualization. However, the bias field artifact can compromise image quality, affecting diagnostic accuracy and quantitative analyses. This study aims to assess the impact of bias field correction on 0.35 T pelvis MRIs by evaluating clinical anatomy visualization and generative adversarial network (GAN) auto-segmentation performance. Materials and methods: 3D simulation MRIs from 60 prostate cancer patients treated on MR-Linac (0.35 T) were collected and preprocessed with the N4ITK algorithm for bias field correction. A 3D GAN architecture was trained, validated, and tested on 40, 10, and 10 patients, respectively, to auto-segment the organs at risk (OARs) rectum and bladder. The GAN was trained and evaluated either with the original or the bias-corrected MRIs. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95th) were computed for the segmented volumes of each patient. The Wilcoxon signed-rank test assessed the statistical difference of the metrics within OARs, both with and without bias field correction. Five radiation oncologists blindly scored 22 randomly chosen patients in terms of overall image quality and visibility of boundaries (prostate, rectum, bladder, seminal vesicles) of the original and bias-corrected MRIs. Bennett's S score and Fleiss' kappa were used to assess the pairwise interrater agreement and the interrater agreement among all the observers, respectively. Results: In the test set, the GAN trained and evaluated on original and bias-corrected MRIs showed DSC/HD95th of 0.92/5.63 mm and 0.92/5.91 mm for the bladder and 0.84/10.61 mm and 0.83/9.71 mm for the rectum. No statistical differences in the distribution of the evaluation metrics were found neither for the bladder (DSC: p = 0.07; HD95th: p = 0.35) nor for the rectum (DSC: p = 0.32; HD95th: p = 0.63). From the clinical visual grading assessment, the bias-corrected MRI resulted mostly in either no change or an improvement of the image quality and visualization of the organs' boundaries compared with the original MRI. Conclusion: The bias field correction did not improve the anatomy visualization from a clinical point of view and the OARs' auto-segmentation outputs generated by the GAN.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

Magnetic resonance imaging for assessment of rectal cancer nodes after chemoradiotherapy: A single center experience.

BACKGROUND: Accurate nodal restaging is becoming clinically more important in patients with locally advanced rectal cancer (LARC) with the emergence of organ-preserving treatment after a good response to neoadjuvant chemoradiotherapy (nCRT). PURPOSE: To evaluate the accuracy of MRI in identifying negative N status (ypN0 patients) in LARC after nCRT. MATERIAL AND METHODS: 191 patients with LARC underwent MRI before and 6-8 weeks after nCRT and subsequent total mesorectal excision. Short-axis diameter of mesorectal lymph nodes was evaluated on the high resolution T2-weighted images to compare MRI restaging with histopathology.. RESULTS: 146 and 45 patients had a negative N status (ypN0) and positive N status (ypN + ), respectively. On restaging MRI, the 70 % reduction in size of the largest node was associated with an area under the curve (AUC) of 0.818 to predict ypN0 stage, with a sensitivity of 93.3 % and a negative predictive value (NPV) of 95.4 %. No nodes were observed in 38 pts (37 pts ypN0 and 1 patient ypN + ), with sensitivity and NPV of nodes disappearance for ypN0 stage of 93.3 % and 92.5 % respectively. A 2.2 mm cut-off in short-axis diameter was associated with an AUC of 0.83 for the prediction of ypN0 nodal stage, with sensitivity and NPV of 79,5% and 91.1 % respectively. CONCLUSION: A reduction in size of 70 % of the largest limph-node on MRI at rectal cancer restaging has high sensitivity and NPV for prediction of ypN0 stage after nCRT. The high NPV of node disappearance and of a ≤ 2.2 mm short-axis diameter is confirmed.

Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.

BACKGROUND AND PURPOSE: This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients. METHODS: Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria. RESULTS: The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. AUTHOR: When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations. CONCLUSIONS: This study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria.

Evaluation of clinical parallel workflow in online adaptive MR-guided Radiotherapy: A detailed assessment of treatment session times.

Introduction: Advancements in MRI-guided radiotherapy (MRgRT) enable clinical parallel workflows (CPW) for online adaptive planning (oART), allowing medical physicists (MPs), physicians (MDs), and radiation therapists (RTTs) to perform their tasks simultaneously. This study evaluates the impact of this upgrade on the total treatment time by analyzing each step of the current 0.35T-MRgRT workflow. Methods: The time process of the workflow steps for 254 treatment fractions in 0.35 MRgRT was examined. Patients have been grouped based on disease site, breathing modality (BM) (BHI or FB), and fractionation (stereotactic body RT [SBRT] or standard fractionated long course [LC]). The time spent for the following workflow steps in Adaptive Treatment (ADP) was analyzed: Patient Setup Time (PSt), MRI Acquisition and Matching (MRt), MR Re-contouring Time (RCt), Re-Planning Time (RPt), Treatment Delivery Time (TDt). Also analyzed was the timing of treatments that followed a Simple workflow (SMP), without the online re-planning (PSt + MRt + TDt.). Results: The time analysis revealed that the ADP workflow (median: 34 min) is significantly (p < 0.05) longer than the SMP workflow (19 min). The time required for ADP treatments is significantly influenced by TDt, constituting 40 % of the total time. The oART steps (RCt + RPt) took 11 min (median), representing 27 % of the entire procedure. Overall, 79.2 % of oART fractions were completed in less than 45 min, and 30.6 % were completed in less than 30 min. Conclusion: This preliminary analysis, along with the comparative assessment against existing literature, underscores the potential of CPW to diminish the overall treatment duration in MRgRT-oART. Additionally, it suggests the potential for CPW to promote a more integrated multidisciplinary approach in the execution of oART.

Auto-segmentation of pelvic organs at risk on 0.35T MRI using 2D and 3D Generative Adversarial Network models.

PURPOSE: Manual recontouring of targets and Organs At Risk (OARs) is a time-consuming and operator-dependent task. We explored the potential of Generative Adversarial Networks (GAN) to auto-segment the rectum, bladder and femoral heads on 0.35T MRIs to accelerate the online MRI-guided-Radiotherapy (MRIgRT) workflow. METHODS: 3D planning MRIs from 60 prostate cancer patients treated with 0.35T MR-Linac were collected. A 3D GAN architecture and its equivalent 2D version were trained, validated and tested on 40, 10 and 10 patients respectively. The volumetric Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95th) were computed against expert drawn ground-truth delineations. The networks were also validated on an independent external dataset of 16 patients. RESULTS: In the internal test set, the 3D and 2D GANs showed DSC/HD95th of 0.83/9.72 mm and 0.81/10.65 mm for the rectum, 0.92/5.91 mm and 0.85/15.72 mm for the bladder, and 0.94/3.62 mm and 0.90/9.49 mm for the femoral heads. In the external test set, the performance was 0.74/31.13 mm and 0.72/25.07 mm for the rectum, 0.92/9.46 mm and 0.88/11.28 mm for the bladder, and 0.89/7.00 mm and 0.88/10.06 mm for the femoral heads. The 3D and 2D GANs required on average 1.44 s and 6.59 s respectively to generate the OARs' volumetric segmentation for a single patient. CONCLUSIONS: The proposed 3D GAN auto-segments pelvic OARs with high accuracy on 0.35T, in both the internal and the external test sets, outperforming its 2D equivalent in both segmentation robustness and volume generation time.

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.

BACKGROUND AND PURPOSE: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. METHODS: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. RESULTS: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. CONCLUSIONS: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients.